Abstract Hyperkalemia (serum potassium >5.0 mEq/l) is a significant complication in patients with heart failure, chronic kidney disease, and diabetes mellitus, particularly when treated with renin-angiotensin-aldosterone system inhibitors (RAASi). Both hyperkalemia and RAASi interruption are associated with increased cardiovascular events, hospitalizations, and mortality. This expert opinion document, developed between January and December 2024 through a systematic process, aims to establish guidance for hyperkalemia treatment in Indonesian patients with cardiorenal diseases receiving RAASi therapy, addressing the unique challenges within the Indonesian healthcare context. A comprehensive literature review of international guidelines and regional studies was conducted by a panel of 11 expert specialists (3 cardiologists, 6 internist-nephrologists, and 2 internist-cardiologists), who evaluated 29 statements covering diagnosis, monitoring, prevention, and treatment of hyperkalemia. Of the 29 statements, 26 reached consensus: 17 statements achieved very high agreement (≥90%) and 9 attained high agreement (≥67% – <90%). The agreed statements covered key areas, including potassium monitoring frequency, RAASi dose optimization strategies, dietary modifications, and treatment thresholds. Three statements regarding alternative therapeutic approaches did not receive agreement (<67%) due to limited local availability and cost considerations. Key recommendations include structured monitoring protocols for high-risk patients, strategies for RAASi dose optimization while managing hyperkalemia risk, and specific interventions adapted to local resources. This document provides a practical approach for managing hyperkalemia in Indonesian patients with cardiorenal diseases while maintaining optimal RAASi therapy, considering local Indonesian healthcare resources and constraints.
Hyperkalemia ; Cardio-Renal Syndrome ; Renin-Angiotensin System ; Indonesia

Introduction: Hyponatremia is the most common electrolyte imbalance in hospitalized patients, associated with increased morbidity and mortality. Tolvaptan effectively raises serum sodium in SIADH. However, concerns regarding rapid overcorrection and safety persist. This study evaluates the efficacy, safety, and real-world usage patterns of tolvaptan in a tertiary care setting. Methodology: A retrospective single-centre observational study was conducted at Hospital Putrajaya using the electronic records of patients treated with tolvaptan from January 2020 to December 2025. Overcorrection was defined as >10 mmol/L increase within 24 hours, and non-response as <4 mmol/L increment at 24 hours. Results: Twenty-one patients were included, with a mean age of 66.7 years; 57% were male. Most (90.5%) received 7.5 mg initially. Mean baseline sodium was 118.1 ± 4.1 mmol/L. Tolvaptan produced rapid correction, with mean sodium increasing to 127.0 mmol/L at 24 hours (mean increment 8.9 mmol/L). Only one patient (4.8%) was a non-responder at 24 hours. Median time to sodium >130 mmol/L was 1 day, with 60% achieving this within 24 hours. At discharge, mean sodium was 130.4 mmol/L. Median length of stay following initiation was 5.5 days. Overcorrection occurred in 23.8% (n = 5), all in the 7.5 mg group, particularly among those with baseline sodium 115–120 mmol/L. No cases of osmotic demyelination syndrome (ODS) were observed. The mean internal for initiation is approximately 6 days from diagnosis. Tolvaptan usage increased and peaked in the first 3 years, but subsequently dropped and plateaued over the last 2 years. Conclusion Tolvaptan is safe and effective for sodium correction; although overcorrection remains a risk, no long-term sequelae of ODS were observed, underscoring the need for vigilant monitoring. Its use in Hospital Putrajaya remains limited, with delayed initiation possibly due to tolvaptan being considered a secondary treatment after failure of other options
Hyponatremia ; Tolvaptan

Introduction: Primary adrenal insufficiency is rare and potentially lifethreatening, with an estimated prevalence of five cases per million in Southeast Asia. Local data remain limited, and diagnosis is frequently delayed due to non-specific clinical manifestations. Widespread use of traditional medication in Malaysia may further undermine recognition, particularly when steroid exposure is concealed. We report a female on prolonged use of traditional remedies presented with classic features of Addison’s disease rather than cushingoid features, confirmed by biochemical results. Case: A 65-year-old female with underlying dyslipidemia and osteoarthritis presented with 4 days of giddiness, poor intake, nausea, and diarrhea. Further history revealed prolonged use of multiple traditional Chinese medicines, discontinued months prior, raising suspicion of prior steroid exposure. She claimed her skin has become darker over the past 2 months. She denied any infectious symptoms, contact with PTB patients, or exposure to birds. There was no family history of autoimmune disease. Clinically, she was dehydrated and hypotensive. Her blood pressure improved after fluid resuscitation. There was hyperpigmentation involving the face, extremities, tongue, and buccal mucosa. Investigation results showed severe hyponatremia (119 mmol/L), hyperkalemia (4.93 mmol/L), with normal creatinine and negative infective markers. Hyponatremia persisted despite adequate hydration. Thyroid function test was normal (Free T4 12.28 pmol/L and thyroid-stimulating hormone 4.16 µIU/mL). Morning cortisol was suppressed (37 nmol/L) with markedly elevated adrenocorticotropic hormone levels (1,134 pg/mL), confirming the diagnosis of primary adrenal insufficiency. Hence, hydrocortisone was commenced, and serum sodium was normalized 2 days later. The underlying etiology remains under evaluation, although autoimmune adrenalitis is the most likely cause. Conclusion Primary adrenal insufficiency should be considered in patients presenting with unexplained hyponatremia and hypotension. In a setting where traditional medication use is prevalent, unrecognized steroid exposure may further complicate diagnosis. A thorough clinical and appropriate biochemical assessment is crucial to differentiating primary from secondary adrenal insufficiency.
Hyponatremia

INTRODUCTION

Despite advancements in surgical techniques aimed at preserving parathyroid function, postoperative hypocalcemia (PoH) remains a challenge following elective total thyroidectomy. Management typically involves postoperative calcium supplementation; however, some studies suggest preoperative calcium and/or vitamin D supplementation may prevent PoH. This paper analyzed existing studies to determine efficacy of preoperative calcium, with or without vitamin D, in preventing hypocalcemia in total thyroidectomy patients. Level of Evidence: Meta-analysis, Level IV.

METHODS

A systematic review and meta-analysis was conducted with PROSPERO Registration No. CRD42024426410. Searches were performed on PubMED, PubMED Central, Embase, Cochrane Library, and HERDIN without date or language restrictions. Relevant studies underwent multiple screenings, with accepted individual studies assessed for bias or quality. Meta-analysis was performed using SPSS version 24.

RESULTS

A total of 345 studies were initially identified. Following deduplication, exclusion, and quality appraisal, 8 studies were included for analysis. Random effects model was utilized for all analysis due to heterogeneity in data. Results indicate that preoperative calcium, with or without vitamin D supplementation, correlated with higher postoperative calcium levels (z = 3.09, p < 0.001), reduced incidence of laboratory (z= 2.05, p = 0.03) and clinical hypocalcemia (z= 2.94, p < 0.001), and shorter hospital stay (z= 2.32, p = 0.01).

CONCLUSION

Results from the conducted meta-analysis support the proposed practice of providing calcium with or without vitamin D supplementation among patients who are to undergo total thyroidectomy procedures to prevent postoperative hypocalcemia.

Human ; Vitamins ; Vitamin D ; Calcium ; Hypocalcemia ; Thyroidectomy

Primary hyperparathyroidism is characterized by increased secretion of parathyroid hormone, leading to hypercalcemia and skeletal and renal complications. In the past, it was diagnosed when presenting with classical signs and symptoms. Currently, the most common clinical presentation of PHPT is asymptomatic hypercalcemia, often detected by routine screening tests. Due to the changing presentations, the diagnosis can become challenging.

We present BA, a 16-year-old female with a 2-year history of multiple fractures, progressive lytic bone lesions and pain, and kidney stones. She was initially managed as a case of polyostotic fibrous dysplasia. The workup also revealed low levels of vitamin D, hypercalcemia, increased alkaline phosphatase, and elevated intact parathyroid hormones. A neck ultrasound revealed two solid masses posterior to the right thyroid lobe.

She underwent right parathyroidectomy, and a biopsy confirmed a double parathyroid adenoma.

This report also highlights the management of the case in a low-resource setting and the importance of timely diagnosis of primary hyperthyroidism to prevent a delay in the management, which could cause unnecessary pain, bone deformities, and disability.

Human ; Female ; Adolescent: 13-18 Yrs Old ; Parathyroid Hormone ; Parathyroid Neoplasms ; Parathyroidectomy ; Phosphoric Monoester Hydrolases ; Fractures, Multiple ; Hypercalcemia ; Hyperparathyroidism ; Hyperthyroidism

McKrittick-Wheelock syndrome refers to a condition characterized by a large rectal mass accompanied by excessive mucoid discharge and associated electrolyte imbalances, including hyponatremia and hypochloremia. This is a benign condition that can unexpectedly lead to serious illness in patients, making it essential for all clinicians to be aware of. We present the case of an 80-year-old female presented with a 4-year history of secretory diarrhea, hematochezia, enlarging fleshy rectal mass with copious mucoid discharge associated with hyponatremia and hypochloremia. Physical examination revealed a polypoid rectal mass secreting copious mucoid discharge with a 2cm base of stalk prolapsing 4cm FAV. The patient underwent rectal excision via trans-anal approach leading to resolution of symptoms. Postoperatively, the patient made a good recovery and was discharged. During follow-up, there was no recurrence of secretory diarrhea. Additionally, the dizziness and other symptoms had resolved. This case emphasizes the importance of recognizing McKittrick-Wheelock syndrome (MWS) when faced with a rectal mass presenting alongside chronic secretory diarrhea and associated electrolyte disturbances. Despite its rare occurrence, clinicians should consider this diagnosis in patients with a rectal mass to avoid delayed treatment and prevent serious complications.

Human ; Female ; Gastrointestinal Hemorrhage ; Hyponatremia ; Diarrhea ; Dizziness

Donors with a serum sodium concentration of >155 mmol/L are extended criteria donors for liver transplantation (LT). Elevated serum sodium of donors leads to an increased incidence of hepatic dysfunction in the early postoperative period of LT; however, the exact mechanism has not been reported. We constructed a Lewis rat model of 70% hepatic parenchymal area subjected to ischemia-reperfusion (I/R) with hypernatremia and a BRL-3A cell model of hypoxia-reoxygenation (H/R) with high-sodium (HS) culture medium precondition. To determine the degree of injury, biochemical analysis, histological analysis, and oxidative stress and apoptosis detection were performed. We applied specific inhibitors of the epithelial sodium channel (ENaC) and Na⁺/Ca²⁺ exchanger (NCX) in vivo and in vitro to verify their roles in injury. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) levels and the area of hepatic necrosis were significantly elevated in the HS+I/R group. Increased reactive oxygen species (ROS) production, myeloperoxidase (MPO)‍-positive cells, and aggravated cellular apoptosis were detected in the HS+I/R group. The HS+H/R group of BRL-3A cells showed significantly increased cellular apoptosis and ROS production compared to the H/R group. The application of amiloride (Amil), a specific inhibitor of ENaC, reduced ischemia-reperfusion injury (IRI) aggravated by HS both in vivo and in vitro, as evidenced by decreased serum transaminases, inflammatory cytokines, apoptosis, and oxidative stress. SN-6, a specific inhibitor of NCX, had a similar effect to Amil. In summary, hypernatremia aggravates hepatic IRI, which can be attenuated by pharmacological inhibition of ENaC or NCX.
Animals ; Reperfusion Injury/drug therapy* ; Hypernatremia/complications* ; Rats ; Liver/metabolism* ; Rats, Inbred Lew ; Male ; Apoptosis ; Sodium-Calcium Exchanger/antagonists & inhibitors* ; Reactive Oxygen Species/metabolism* ; Oxidative Stress ; Epithelial Sodium Channel Blockers/pharmacology* ; Epithelial Sodium Channels ; Cell Line ; Liver Transplantation

Panax species are mostly valuable medicinal plants. While some species' seeds are sensitive to dehydration, the dehydration tolerance of seeds from other Panax species remains unclear. The phospholipase D(PLD) gene plays an important role in plant responses to dehydration stress. However, the characteristics of the PLD gene family and their mechanisms of response to dehydration stress in seeds of Panax species with different dehydration tolerances are not well understood. This study used seeds from eight Panax species to measure the germination rates and PLD activity after dehydration and to analyze the correlation between dehydration tolerance and seed traits. Bioinformatics analysis was also conducted to characterize the PnPLD and PvPLD gene families and to evaluate their expression patterns under dehydration stress. The dehydration tolerance of Panax seeds was ranked from high to low as follows: P. ginseng, P. zingiberensis, P. quinquefolius, P. vietnamensis var. fuscidiscus, P. japonicus var. angustifolius, P. japonicus, P. notoginseng, and P. stipuleanatus. A significant negative correlation was found between dehydration tolerance and seed shape(three-dimensional variance), with flatter seeds exhibiting stronger dehydration tolerance(r=-0.792). Eighteen and nineteen PLD members were identified in P. notoginseng and P. vietnamensis var. fuscidiscus, respectively. These members were classified into five isoforms: α, β, γ, δ, and ζ. The gene structures, subcellular localization, physicochemical properties, and other characteristics of PnPLD and PvPLD were similar. Both promoters contained regulatory elements associated with plant growth and development, hormone responses, and both abiotic and biotic stress. During dehydration, the PLD enzyme activity in P. notoginseng seeds gradually increased as the water content decreased, whereas in P. vietnamensis var. fuscidiscus, PLD activity first decreased and then increased. The expression of PLDα and PLDδ in P. notoginseng seeds initially increased and then decreased, whereas in P. vietnamensis var. fuscidiscus, the expression of PLDα and PLDδ consistently decreased. In conclusion, the dehydration tolerance of Panax seeds showed a significant negative correlation with seed shape. The dehydration tolerance in P. vietnamensis var. fuscidiscus and dehydration sensitivity of P. notoginseng seeds may be related to differences in PLD enzyme activity and the expression of PLDα and PLDδ genes. This study provided the first systematic comparison of dehydration tolerance in Panax seeds and analyzed the causes of tolerance differences and the optimal water content for long-term storage at ultra-low temperatures, thus providing a theoretical basis for the short-term and ultra-low temperature long-term storage of medicinal plant seeds with varying dehydration tolerances.
Seeds/metabolism* ; Panax/physiology* ; Plant Proteins/metabolism* ; Gene Expression Regulation, Plant ; Phospholipase D/metabolism* ; Plants, Medicinal/enzymology* ; Germination ; Multigene Family ; Water/metabolism* ; Dehydration ; Phylogeny

Dyskinesia-hyperpyrexia syndrome（DHS）is an acute hyperpyrexia syndrome that is different from Parkinsonism-hyperpyrexia syndrome and serotonin syndrome in patients with advanced Parkinson's disease（PD），with the main symptoms of high fever，disturbance of consciousness，elevated creatine kinase，and dyskinesia. Syndrome of inappropriate secretion of antidiuretic hormone（SIADH）is a clinical syndrome caused by excessive secretion of antidiuretic hormone，which leads to the symptoms of dilutional hyponatremia，water retention，and increases in urine sodium and urine osmotic pressure. DHS has not received widespread attention in clinical practice，and there are rare reports of DHS comorbid with SIADH. This article reports the diagnosis and treatment processes of a case of DHS comorbid with SIADH and reviews the relevant literature，in order to guide the diagnosis and treatment of PD-related critical diseases.
Hyponatremia

Objective: To investigate dose-response associations between fluid overload (FO) and hospital mortality in patients with sepsis. Methods: The current cohort study was prospective and multicenter. Data were derived from the China Critical Care Sepsis Trial, which was conducted from January 2013 to August 2014. Patients aged≥18 years who were admitted to intensive care units (ICUs) for at least 3 days were included. Fluid input/output, fluid balance, fluid overload (FO), and maximum FO (MFO) were calculated during the first 3 days of ICU admission. The patients were divided into three groups based on MFO values: MFO<5%L/kg, MFO 5%-10%L/kg, and MFO≥10% L/kg. Kaplan-Meier analysis was used to predict time to death in hospital in the three groups. Associations between MFO and in-hospital mortality were evaluated via multivariable Cox regression models with restricted cubic splines. Results: A total of 2 070 patients were included in the study, of which 1 339 were male and 731 were female, and the mean age was (62.6±17.9) years. Of 696 (33.6%) who died in hospital, 968 (46.8%) were in the MFO<5%L/kg group, 530 (25.6%) were in the MFO 5%-10%L/kg group, and 572 (27.6%) were in the MFO≥10%L/kg group. Deceased patients had significantly higher fluid input than surviving patients during the first 3 days [7 642.0 (2 874.3, 13 639.5) ml vs. 5 738.0 (1 489.0, 7 153.5)ml], and lower fluid output [4 086.0 (1 367.0, 6 354.5) ml vs. 6 130.0 (2 046.0, 11 762.0) ml]. The cumulative survival rates in the three groups gradually decreased with length of ICU stay, and they were 74.9% (725/968) in the MFO<5% L/kg group, 67.7% (359/530) in the MFO 5%-10%L/kg group, and 51.6% (295/572) in the MFO≥10%L/kg group. Compared with the MFO<5%L/kg group, the MFO≥10%L/kg group had a 49% increased risk of inhospital mortality (HR=1.49, 95%CI 1.28-1.73). For each 1% L/kg increase in MFO, the risk of in-hospital mortality increased by 7% (HR=1.07, 95% CI 1.05-1.09). There was a"J-shaped"non-linear association between MFO and in-hospital mortality with a nadir of 4.1% L/kg. Conclusion: Higher and lower optimum fluid balance levels were associated with an increased risk of in-hospital mortality, as reflected by the observed J-shaped non-linear association between fluid overload and inhospital mortality.
Humans ; Male ; Female ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Hospital Mortality ; Cohort Studies ; Prospective Studies ; Water-Electrolyte Imbalance ; Sepsis ; Intensive Care Units ; Retrospective Studies